Delivery systems or encapsulation systems are used in various industries to protect active ingredients or to control their release. For instance, in the food industry they are often used to protect flavors, in particular against losses of liquid or volatile components (i) during storage prior to incorporation into the food products, (ii) during mixing of the flavor component with the other food ingredients, (iii) during food processing, such as cooking and baking, (iv) during transportation and storage and (v) during the preparation of the food product by the end-consumer.
Similarly, in the nutraceutical industry, they are often used to protect oxygen-sensitive active material, such as fish oils rich in polyunsaturated fatty acids, by providing an oxygen barrier around the material.
In the flavor and fragrance industry it is known to encapsulate flavors and perfumes so that their release can be controlled according to the needs of the end application.
In all of these applications, the delivery system has the primary object of protecting the sensitive liquid or volatile active ingredient against, for instance, evaporation, degradation or migration, or delaying the release rate of the active ingredient into a desired medium.
Various delivery systems are known that achieve one or more of these object, such as extruded granular delivery systems, for instance. Extruded systems are often formed by melt-extrusion and typically comprise a matrix material or carrier material for a material, product or ingredient that is encapsulated. The matrix material is often described as “viscous” or “rubbery” during the extrusion process and “glassy” in the finished product.
It is recognised by many experts in the field that, in the glassy state, all molecular translation is halted and it is this which provides effective entrapping of the flavor volatiles and prevention of other chemical events such as oxidation. Conversely, in the viscous state, the encapsulation of materials, products and ingredients is less effective in preventing leakage of the encapsulated material.
Thus, glassy matrices have to be produced very carefully to achieve the desired properties.
As an alternative to glassy matrices, it is known to encapsulate active ingredients using crystalline matrices. A well documented process for crystalline encapsulation is co-crystallisation in which an active ingredient becomes embedded in a agglomerate of macro- or microscopic crystals. Numerous publications describing this technology exist, such as Zeller et al., Trends in Food Science & Technology 9 (1999) 389-94; Madene et al. International Journal of Food Science & technology 41 (2006) 1-21); Food Technology, 47, 146-148 (1993); Food Technology, 42, 87-90. 1988; and International Sugar Journal, 96, 493-494. 1994.
U.S. Pat. No. 4,338,350 (Chen et al) describes co-crystallization and refers to concentrating a sucrose solution to the range of 95 to 97%, cooling slightly to create a supersaturated solution, mixing in a second active ingredient (such as a flavor oil), and then vigorously agitating the mixture to cause the sucrose to spontaneously crystallize with the inclusion or entrapment of the active. Thus in this process, crystallization, conglomerate formation, active entrapment, and water volatilization all occur more or less simultaneously within the agitation step making the overall process more difficult to control and optimize.
This difficulty is recognised in Food Technology, 42, 87-90. 1988 where it is stated that the process requires proper control of the rates of nucleation and crystallization, and thermal balance during all of the various phases of the process
A similar co-crystallization process for encapsulated orange peel oil is also disclosed in LWT—Food Science and Technology 29, 645-647, 1996. This describes how 100 g to 250 g of orange peel oil can be incorporated per kg of sugar but that, while the product is granular and easy to handle, the flavor oxidizes readily on subsequent storage and addition of an antioxidant is necessary to protect the flavor. The porous structure of the agglomerates apparently leads to flavor oxidation.
Thus, it would be desirable to provide a crystalline encapsulation system which addresses one or more of these drawbacks. It would be especially desirable to increase the ability to control the process more precisely. It would also be desirable to avoid or at least minimise the porosity of the structure so as to better protect labile or sensitive active ingredients.
Other crystalline entrapments systems are also known. For instance, U.S. Pat. No. 2,566,410 (Griffin) describes a process for creating a solidified composition of a continuous crystalline sorbitol phase and a dispersed essential oil phase. The essential oil is described as “so thoroughly coated and entrapped that loss of said oil from the mass occurred at a negligible rate.” However, unseeded crystallization of sorbitol is known to be a time consuming process taking up to several days (Szatisz J. Therm. Anal. 12 (1977) 351-360) which is an obvious drawback for any commercial application.
U.S. Pat. No. 2,904,440 (Dimick et al) also relates to sorbitol encapsulation where the water and low molecular weight alcohols are removed from a flavoring agent prior to incorporation in molten sorbitol. This is said to remove constituents that interfere in the crystallization process and extend the use of the technology to other systems such as fruit essences. However, this requires additional steps in the process. Further, the sorbitol melt needs to be supercooled prior to adding flavor and seed crystals. Finally, the solidified product needs to be ground into granular particles.
U.S. Pat. No. 4,388,328 (Glass) employs a mixture of sorbitol, saccharine and mannitol as the entrapping medium. Mannitol and saccharin are believed to lower the crystallization temperature of sorbitol to below 70° C. rendering the process advantageous for incorporating volatile flavor compounds. The melt-emulsion could be cast while liquid as a sheet or formed into tablets or droplets with a mold. To create smaller particles solidified sheets are ground and passed through a mess screen.
Nevertheless, generating particles by grinding inevitably leads to a loss of active ingredient at the surface where ground and so it would be desirable to address this problem.
U.S. Pat. No. 6,083,438 describes a process for preparing a composition suitable for use as an excipient for tabletting comprising following steps of (a) mixing of erythritol and sorbitol in a dry form, (b) heating to a temperature where the mixed products are melted, (c) cooling the product, (d) milling the cooled product to obtain a composition having a desired particle size. Milling suffers from the same drawbacks as grinding.
It is also known to use mannitol, a typically crystalline material, in flavor encapsulation. In U.S. Pat. No. 3,314,803 (Dame et al) acetaldehyde is incorporated into mannitol solids through spray drying a super-saturated solution of mannitol. However, this process requires great care in drying the super-saturated solution to avoid completely volatilizing the acetaldehyde or forming a non-entrapping dried mannitol composition. In EP-A1-0497439, erythritol is spray-dried to provide conveniently sized crystals in the form of a free-flowing powder.
However, in both cases, such heating is potentially detrimental since it encourages the loss of liquid or volatile active ingredients.
It would thus be desirable to address this problem.
Encapsulation of active ingredients by spray chilling is described in U.S. Pat. No. 5,525,367 where the carrier for the active ingredient is a high melting-point edible solid such as a hydrogenated vegetable oil, a stearin, or an edible wax. However, such carriers do not always provide a sufficient barrier to prevent hydrophobic active ingredients from leaking from the capsules.
In US-A1-2009/0142401 (Appel et al) spray-congealing is used to form multiparticles of low-solubility drugs and carriers that result in rapid release of the drug. The carrier may be a sugar alcohol such as mannitol or erythritol, and the particles may be prepared by atomisation. The amount of water needs to be sufficient to dissolve the sugar alcohol and the only numbers disclosed are 60%, 55% and 50% water. This water is driven off by heating which, as identified above, is a critical driver of the loss of the active ingredients.
Thus, it is an object of the present invention to address one or more of the problems and/or to provide one or more of the solutions mentioned above.